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A Gradual Increase in Blood Pressure from Early Adulthood to Middle Age May Reduce Brain Health

Individuals with moderate to high levels of blood pressure in young adulthood who experienced a gradual increase in blood pressure through the midlife years had an increased risk for poor brain health, according to a study published on JAMA Network Open on March 10.

Prior studies have reported on the association of elevated blood pressure in midlife and the risk for hypertension, cognitive impairment and dementia, as well as cerebrovascular disease in the later years. But, the study authors noted, until now little was known about the trajectories of blood pressure over time from young adulthood through the middle-aged years and risk for brain disease.

 “Examining the association of young adulthood to midlife blood pressure trajectories with brain integrity in midlife may provide insight into windows of opportunity for intervention and point to subgroups that may be at higher risk for later cognitive impairment," wrote the lead study author Lenore J. Launer, PhD, a senior investigator in the laboratory of epidemiology and population sciences at the National Institute on Aging, and colleagues.

To determine if blood pressure trajectories in early adulthood are associated with brain structure in midlife, the researchers analyzed data from Coronary Artery Risk Development in Young Adults (CARDIA), a multicenter, longitudinal cohort study of 5,115 healthy Black and White adults from Chicago; Minneapolis; Birmingham, Alabama; and Oakland, California. Each participant underwent eight follow-up examinations over the course of 30 years (1985-1986 to 2015-2016) and 853 participants underwent brain MRI analyses; 46.8 percent of them were men, 58.5 percent were White, and 41.5 percent were Black.

The study authors used group-based trajectory modeling to identify five 25-year blood pressure trajectories for three blood pressure traits in the total CARDIA participants with three or more blood pressure measures, which were then applied to analyses of the subset of the 853 participants who underwent MRIs.

The investigators evaluated mean arterial pressure (MAP) as an integrative measure of systolic and diastolic blood pressure. Using linear regression, they examined associations of the blood pressure trajectories with brain structures, adjusting sequentially for demographics, cardiovascular risk factors, and antihypertensive medication use.

They divided the participants into five groups: participants who maintained low blood pressure levels throughout the study period (low-stable); those who started at moderate blood pressure levels and had gradual increases (moderate-gradual); those who started at moderate blood pressure levels and had a more rapid increase (moderate-increasing); individuals who started at a relatively higher blood pressure that was stable throughout the follow-up period (elevated-stable), and those who started at a relatively elevated level, gradually increasing until the age of 40 years, and then moderately decreased (elevated-increasing).

Of 187 individuals,  21.1 percent were in the low-stable group, 43.5 percent were moderate-gradual, 8.0 percent were moderate-increasing, 23.1 percent were elevated-stable, and 4.3 percent were in the elevated increasing group.

The researchers found that compared with blood pressure trajectories that captured low levels and stable trajectories from young adulthood to middle age, participants with trajectories that exhibited a gradual increase in MAP (i.e., moderate-increasing and elevated-increasing) were more likely to experience poor brain health.

Individuals in the moderate increasing and elevated-increasing groups were more likely to have higher abnormal white matter volume (moderate: β, 0.52; elevated: β, 0.57). After adjusting for socio-demographics and cardiovascular risk factors, participants in the MAP elevated-increasing group had lower gray matter cerebral blood flow (β, –0.42).

Those in the elevated-stable group also scored relatively worse on executive function and verbal memory than individuals in the low-stable group. In addition, they found that at-risk groups (i.e., moderate-increasing and elevated-increasing) were comprised disproportionately of a higher number of Black participants.

“It is known that Black individuals have higher rates of hypertension, and exposure to risk factors for hypertension, such as disparities in socioeconomic environments and access to health care, may play a role," the study authors wrote. “Further mechanistic studies with larger samples are needed to investigate whether race, sex, or other socio-behavioral factors modulate the effect of blood pressure trajectory on brain outcomes."

After adjusting for antihypertensive medication use, the difference was consistent for abnormal white matter volume, but the results were no longer significant for gray matter cerebral blood flow.

“Even though our results suggest that the adverse associations of increasing blood pressure with brain outcomes were not significant after adjustment of antihypertensive medication use, future work incorporating a time-varying design is needed to confirm the modulating effect of antihypertensive medication," the researchers wrote.

The study authors noted that as hypertension among young adults increases, additional longitudinal studies with repeated MRI imaging is needed to develop more precise treatments for this population.

“This study showed that moderate-increasing and elevated-increasing blood pressure trajectories during early adulthood are associated with differences in structural brain outcomes as early as midlife," concluded the study authors. “Taken together with evidence from late-life studies, preventing blood pressure increases during young adulthood to middle age may be a promising strategy for prevention of dementia."

Limitations of the study included the inclusion of participants with only three out of eight blood pressure measurements, the modulatory effect of sex or race on the association between trajectory group and brain outcomes was not examined, and the MRI sample used was a healthier group and included fewer Black participants.  

No disclosures were reported.

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Launer L, Hu YH, Halstead M, et al. Association of early adulthood 25-year blood pressure trajectories with cerebral lesions and brain structure in midlife. JAMA Netw Open 2022; Epub 2022 Mar 10.